TY - JOUR
T1 - Acute exposure to environmentally relevant concentrations of phenytoin damages early development and induces oxidative stress in zebrafish embryos
AU - Cardoso-Vera, Jesús Daniel
AU - Gómez-Oliván, Leobardo Manuel
AU - Islas-Flores, Hariz
AU - García-Medina, Sandra
AU - Orozco-Hernández, José Manuel
AU - Heredia-García, Gerardo
AU - Elizalde-Velázquez, Gustavo Axel
AU - Galar-Martínez, Marcela
AU - SanJuan-Reyes, Nely
N1 - Publisher Copyright:
© 2022 Elsevier Inc.
PY - 2022/3
Y1 - 2022/3
N2 - Phenytoin (PHE) is an antiepileptic drug that has been widely used in clinical practice for about 80 years. It is mainly used in the treatment of tonic-clonic and partial seizures. The widespread consumption of this drug around the world has led to PHE being introduced into water bodies through municipal, hospital, and industrial effluent discharges. Since the toxic effects of this drug on aquatic species has been scarcely explored, the aim of this work was to investigate the influence of low (25–400 ngL−1) and high (500–1500 ngL−1) environmentally relevant concentrations of PHE on the development and oxidative status of zebrafish (Danio rerio) embryos. The toxicity of PHE was evaluated from 12 to 96 h after fertilization in D. rerio at concentrations between 25 and 1500 ngL−1. In both the control group and the 0.05% DMSO system, no malformations were observed, all embryos developed normally after 96 h. The severity and frequency of malformations increased with increasing PHE concentration compared to embryos in the control group. Malformations observed included developmental delay, hypopigmentation, miscellaneous (more than one malformation in the same embryo), modified chorda structure, tail malformation, and yolk deformation. Concerning the biomarkers of oxidative stress, an increase in the degree of lipid peroxidation, protein carbonylation, and hydroperoxide content was observed (p < 0.05) concerning the control. In addition, a significant increase (p < 0.05) in antioxidant enzymes (SOD, CAT, and GPx) was observed at low exposure concentrations (25–400 ngL−1), with a decrease in enzyme activity at high concentrations (500–1500 ngL−1). Our IBR analysis demonstrated that oxidative damage biomarkers got more influence at 500ngL−1 of PHE. The results demonstrated that PHE may affect the embryonic development of zebrafish and that oxidative stress may be involved in the generation of this embryotoxic process.
AB - Phenytoin (PHE) is an antiepileptic drug that has been widely used in clinical practice for about 80 years. It is mainly used in the treatment of tonic-clonic and partial seizures. The widespread consumption of this drug around the world has led to PHE being introduced into water bodies through municipal, hospital, and industrial effluent discharges. Since the toxic effects of this drug on aquatic species has been scarcely explored, the aim of this work was to investigate the influence of low (25–400 ngL−1) and high (500–1500 ngL−1) environmentally relevant concentrations of PHE on the development and oxidative status of zebrafish (Danio rerio) embryos. The toxicity of PHE was evaluated from 12 to 96 h after fertilization in D. rerio at concentrations between 25 and 1500 ngL−1. In both the control group and the 0.05% DMSO system, no malformations were observed, all embryos developed normally after 96 h. The severity and frequency of malformations increased with increasing PHE concentration compared to embryos in the control group. Malformations observed included developmental delay, hypopigmentation, miscellaneous (more than one malformation in the same embryo), modified chorda structure, tail malformation, and yolk deformation. Concerning the biomarkers of oxidative stress, an increase in the degree of lipid peroxidation, protein carbonylation, and hydroperoxide content was observed (p < 0.05) concerning the control. In addition, a significant increase (p < 0.05) in antioxidant enzymes (SOD, CAT, and GPx) was observed at low exposure concentrations (25–400 ngL−1), with a decrease in enzyme activity at high concentrations (500–1500 ngL−1). Our IBR analysis demonstrated that oxidative damage biomarkers got more influence at 500ngL−1 of PHE. The results demonstrated that PHE may affect the embryonic development of zebrafish and that oxidative stress may be involved in the generation of this embryotoxic process.
KW - Antiepileptic drugs
KW - Embryotoxicity
KW - Oxidative stress
KW - Teratogenesis
KW - Zebrafish
UR - http://www.scopus.com/inward/record.url?scp=85122244029&partnerID=8YFLogxK
U2 - 10.1016/j.cbpc.2021.109265
DO - 10.1016/j.cbpc.2021.109265
M3 - Artículo
C2 - 34990834
AN - SCOPUS:85122244029
SN - 1532-0456
VL - 253
JO - Comparative Biochemistry and Physiology - C Toxicology and Pharmacology
JF - Comparative Biochemistry and Physiology - C Toxicology and Pharmacology
M1 - 109265
ER -